Kenner, et al. J. Chem. Soc. 673-678 (1953) describes a C-terminal degradation experiment which required 110 hours to quantitatively form a thiohydantoin amino acid. Bailey U.S. Pat. No. 5,180,807 describes an improvement in which diphenyl phosphoroisothiocyanatidate is used concurrently with a heterocyclic amine, such as pyridine.
Application Ser. No. 08/094,024 illustrates sequential use of diphenyl phosphoroisothiocyanatidate and a heterocyclic amine for C-terminal peptide degradation. In a first step, the peptide which is preferably bound to a solid phase is converted to a carboxylate salt by triethylamine or similar base. In a second step, the carboxylate is reacted with diphenyl phosphoroisothiocyanatidate. In a third step, a heterocyclic amine such as pyridine is added.